An ultra-rare genetic condition

Your child or patient has
the AKT2 E17K (p.Glu17Lys) mutation. So do (at least) 12 others.
Let's connect.

We're connecting every family, clinician and researcher who knows this condition — to share what works and push toward better treatments.

Child playing with a DNA toy
13
known patients worldwide
12 published cases · view case reports →
1–38
age range of known patients
youngest: 1 yr · oldest: 38 yrs
4+
therapeutic directions being explored or proposed

This initiative was started by a family and their research team. Together, we believe that connecting the handful of families, clinicians, and researchers who know this condition — across whatever distance separates them — is the fastest path to better understanding, better care, and better treatments. More about us →

About the condition

A mutation that keeps a key
metabolic pathway switched on.

AKT2 E17K (formerly known as MORFAN syndrome) causes the AKT2 protein to remain constitutively active — leading to severe fasting hypoglycemia despite very low insulin levels. The genetic cause is known and the mechanism is well understood. That matters enormously for the path to treatment.

Full explanation of the condition
Research & hope

The science is moving.
Here's the frontier.

From nutritional management to targeted drug therapy — multiple paths are being actively explored. Including one that could address the mutation itself.

Precision genetic therapies — addressing the mutation at its source
Early research is underway to evaluate whether an antisense oligonucleotide (ASO) approach could help reduce disease-causing AKT2 activity. This work is at an early stage and not yet an available treatment. Gene editing via CRISPR remains a theoretical possibility.
ASO - preliminary inquiry underway CRISPR emerging mTOR inhibitors reported Glucagon-based therapies promising
Full treatment options overview
Living with AKT2 and FAQs

What families and clinicians
have learned.

Practical knowledge that no paper captures — from nutrition and monitoring to development and long-term outlook. Growing with every family that joins the network.

🍽️
Nutrition & hypoglycemia
Fasting tolerance, cornstarch therapy, Glycosade — what families have found.
🧠
Development & presentation
Why patients present differently — and what we know about long-term outcomes.
All questions & answers

There are only a handful of families
in the world who understand this.

This network exists to find all of them — and connect them with the clinicians and researchers who can help.

👨‍👩‍👧 Families
Parents and caregivers — your experience is knowledge no paper has captured
🩺 Clinicians
Endocrinologists, geneticists, dietitians who've encountered this condition
🔬 Researchers
Scientists working on AKT2, PI3K/mTOR pathways, or related rare disorders
About the Condition

AKT2 E17K (p.Glu17Lys) —
understanding the biology

A rare gain-of-function mutation that keeps a key metabolic pathway switched on.

The condition

What is AKT2 E17K?

AKT2 E17K (formerly known as MORFAN syndrome) is a rare genetic condition caused by an activating mutation in the AKT2 gene. The disease-causing variant, p.Glu17Lys (E17K), results in a gain-of-function, meaning the AKT2 protein becomes active even when it should be switched off. This leads to constitutive, insulin-independent activation of the AKT2 signaling pathway — one of the key pathways responsible for regulating glucose metabolism and cellular growth.

Under normal circumstances, insulin activates AKT2 after a meal, signaling tissues such as muscle and fat to take up glucose from the bloodstream. As blood glucose levels fall, insulin secretion decreases and the pathway becomes inactive. In people with AKT2 E17K, however, AKT2 remains partially active even when insulin levels are very low or undetectable. As a result, tissues continue to behave as though insulin is present, removing glucose from the bloodstream and suppressing the body's normal fasting response.

This abnormal signaling explains one of the most distinctive features of the condition: severe fasting hypoglycemia despite low insulin levels. During hypoglycemia, the body would normally switch to alternative energy sources by releasing fatty acids and producing ketones. Because the AKT2 pathway remains active, these protective responses may be reduced, resulting in the characteristic biochemical pattern often seen in affected individuals: hypoketotic, hypofattyacidemic, hypoinsulinemic hypoglycemia.

This condition was first described in 1993 under the name MORFAN syndrome — an acronym for Mental retardation, pre- and post-natal Overgrowth, Remarkable Face, and Acanthosis Nigricans, the cluster of features observed in the original case report. Over the following two decades, additional cases with this same clinical pattern were identified and eventually linked to an activating mutation in AKT2. As genetic testing has made it possible to diagnose the condition by its underlying genetic cause rather than its clinical features alone, the medical literature has moved toward describing it as AKT2 E17K, and the MORFAN name is now considered largely outdated.

Although the condition is extremely rare, understanding of its biological mechanism has advanced considerably over the past decade. The identification of a specific genetic cause and a well-defined signaling pathway has opened the door to targeted therapeutic approaches and provides a strong foundation for future research.

Clinical features

What has been reported
in affected individuals?

Not every patient develops all of these features, and severity varies considerably between individuals. Although all patients share the same AKT2 mutation, the clinical presentation can differ substantially from one person to the next and can change over the person's lifetime.

Hypoinsulinemic hypoglycemia
Low blood glucose occurring without elevated insulin — the hallmark feature
Hypoglycemic seizures
Seizures triggered by dangerously low blood glucose levels
Developmental delay
May be related to hypoglycemia severity, not necessarily the mutation itself — see FAQ →
Hemihypertrophy
Asymmetric overgrowth, where one side of the body is larger than the other
Overgrowth / Macrosomia
Increased overall body or tissue size beyond normal range
Proptosis
Forward displacement of the eye, causing a bulging appearance
Macroglossia
Enlargement of the tongue beyond normal size
Acanthosis nigricans
Dark, velvety patches of skin, typically in body folds and creases
Why does presentation vary?

Researchers do not yet fully understand why some individuals are more severely affected than others. One possible explanation is mosaicism — where different tissues carry different proportions of cells affected by the mutation. Other factors, including genetic background, disease severity, and differences in medical management, may also play a role.

Diagnosis

How is AKT2 E17K diagnosed?

The diagnosis is confirmed through genetic testing. Before genetic testing is performed, many patients come to medical attention because of recurrent hypoglycemia. During a hypoglycemic episode, blood tests may show the characteristic pattern of hypoketotic, hypofattyacidemic, hypoinsulinemic hypoglycemia, which can raise suspicion for abnormal activation of the AKT2 pathway.

Each patient matters

Only a small number of patients have been reported in the medical literature worldwide. Each newly identified patient may contribute valuable knowledge to families, clinicians, and researchers everywhere.

Treatments and Hope

The science is moving.
Here's the frontier.

Multiple therapeutic directions are being actively explored — from managing symptoms to targeting the mutation itself. The landscape is broader than any single group, and that's exactly why connecting matters.

The website was reviewed for medical and scientific accuracy by Dr. Shai Fuchs, MD, PhD and Dr. Michael Shulman, MD, BEng from Sheba Medical Centre. The information provided on this website does not constitute medical advice and is meant for community building and research purposes only. All medical decisions belong to your own treatment team.
Where we are today

Current management

Today, most people with AKT2 E17K (p.Glu17Lys) are managed through nutritional strategies aimed at preventing hypoglycemia. While these approaches can be effective, they do not address the underlying genetic cause of the condition.

🍽️
Standard supportive care
Nutritional management
Care is individualized to prevent hypoglycemia and may include frequent meals, overnight tube feeding, uncooked cornstarch or a modified starch preparation. Responses differ between patients; published experience with modified starch includes both benefit and lack of benefit. The feeding plan should be tailored and monitored by the treating team.
Therapeutic approaches being explored
Reported in AKT2 patients
Sirolimus (mTOR inhibition)
Small case reports describe improved glucose control in some people with AKT2 E17K treated with sirolimus, a medicine that inhibits mTOR signaling. These observations are encouraging, but do not establish how well it works across patients or its long-term safety. Sirolimus does not correct the mutation and requires specialist supervision because of potential adverse effects.
Does not correct the underlying mutation · May require long-term treatment · Potential side effects can limit its use in children
Promising — being explored in AKT2
Glucagon-based therapies
Glucagon can raise blood glucose by increasing glucose release from the liver. Some published AKT2 E17K cases have shown a rise in glucose after a glucagon challenge. Dasiglucagon delivered by continuous subcutaneous infusion has been studied in children with congenital hyperinsulinism, while a published case report describes treatment with the long-acting analogue efpegerglucagon in glucokinase-related hyperinsulinism. These are different conditions, which cannot be automatically assumed to apply to AKT2 E17K, yet represent a path we view as worth pursuing.
We are looking into whether glucagon-based approaches could have a role in managing AKT2 E17K-related hypoglycemia. Their suitability, safety and longer-term benefit in this condition require further evaluation.
The most exciting frontier
Precision genetic therapies —
addressing the mutation itself
Rather than controlling symptoms, these approaches aim to reduce or eliminate the activity of the disease-causing AKT2 mutation itself — at its source.

A known disease-causing variant provides a starting point for research, but delivering a treatment to the relevant tissues and establishing safety remain major challenges. Two approaches are particularly compelling:

Antisense Oligonucleotides (ASO)
Antisense oligonucleotides (ASOs) are short synthetic molecules that act on RNA to change protein production. Our lab and partnering labs at Sheba have begun early research toward evaluating whether an ASO approach could help reduce disease-causing AKT2 activity in AKT2 E17K. This work is at an early stage. Selectivity, delivery, safety and potential benefit remain to be established; an ASO treatment for this condition is not currently available through this work.
Gene editing (CRISPR)
Technologies that may allow direct correction or inactivation of the disease-causing mutation. Liver-targeted gene editing is advancing rapidly, with recent real-world applications in other rare genetic conditions — making this an increasingly realistic, though still theoretical, direction for AKT2 E17K.
ASO - preliminary inquiry underway
Why researchers are optimistic
  • The genetic cause is known and the mechanism is increasingly well understood
  • Case reports show that patients can respond to interventions that target the underlying biology
  • It is worth exploring whether continuous subcutaneous glucagon infusion can prevent AKT2 E17K-related hypoglycemia in patients that demonstrate a response to a glucagon challenge
  • New genetic medicine platforms — including ASO and CRISPR — are advancing rapidly, and early-stage ASO research for AKT2 E17K is now underway
  • Each newly identified patient adds meaningful knowledge to the field
  • Many questions remain unanswered, but there are clear scientific paths worth pursuing
Collaboration matters

Because AKT2 E17K is so rare, no single team has the full picture. Other families may be pursuing therapeutic approaches we haven't explored. This network exists to bring all of that together.

Living with AKT2 and FAQs

What families and clinicians
have learned.

Practical knowledge that doesn't appear in any paper — gathered from families and clinicians who live and work with this condition every day.

1. Understanding AKT2 E17K (p.Glu17Lys)

What is AKT2 E17K? ▾

AKT2 E17K is an ultra-rare genetic mutation affecting the AKT2 gene, which plays an important role in insulin signaling and glucose metabolism.

The mutation causes the AKT2 pathway to remain active even when insulin levels are low, leading to increased glucose uptake by tissues and an increased risk of hypoglycemia.

How is the AKT2 E17K mutation inherited? ▾

In most reported cases, AKT2 E17K occurs as a de novo mutation — meaning it arises spontaneously and is not inherited from either parent.

In at least one reported family, however, the mutation was inherited from a father who was a mosaic for the variant in his sperm only. In this case, the father carried the mutation in only a portion of his reproductive cells, allowing him to pass on the mutation. However, he did not exhibit symptoms of the syndrome himself because the mutation was not present in the somatic (non-reproductive) cells of his body.

What is the difference between AKT2 E17K and MORFAN syndrome? ▾

They refer to the same underlying condition. MORFAN syndrome was the name given in 1993 to a cluster of features observed in an early case — mental retardation (an older clinical term for developmental delay/intellectual disability), pre- and post-natal overgrowth, remarkable face, and acanthosis nigricans — at a time when the genetic cause was not yet known.

This kind of feature-based naming was the standard approach in genetics before genetic testing became widely available, and it laid important groundwork for later researchers. As more cases were identified and genetic testing advanced, researchers discovered that not everyone with the same underlying AKT2 mutation shared the same combination of clinical features.

Therefore, the field has since moved toward naming the condition by its specific genetic mutation, AKT2 E17K, which allows for a more precise and consistent diagnosis.

Why does AKT2 E17K cause hypoglycemia? ▾

AKT2 (AKT serine/threonine kinase 2) is a key enzyme in the biological pathway through which insulin signals cells to remove glucose from the bloodstream and use it as an energy source.

In people with the p.Glu17Lys mutation, this signaling pathway is overactive even in the absence of normal insulin stimulation. As a result, glucose is removed from the bloodstream more readily, increasing the risk of hypoglycemia, particularly during fasting.

How is AKT2 E17K diagnosed? ▾

The diagnosis is confirmed through genetic testing.

Before genetic testing is performed, many patients come to medical attention because of recurrent hypoglycemia. During a hypoglycemic episode, blood tests may show a characteristic pattern known as hypofattyacidemic, hypoinsulinemic, hypoglycemia, which can raise suspicion for abnormal activation of the AKT2 pathway.

How rare is this condition? ▾

AKT2 E17K is considered an ultra-rare genetic condition. Only 12 patients have been reported in the medical literature worldwide.

As a result, many aspects of the condition remain incompletely understood, and each newly identified patient may contribute valuable knowledge to families, clinicians, and researchers.

What clinical features have been reported? ▾

Published reports have described a range of features. Not every patient develops all of these, and severity varies considerably between individual patients and throughout a patient’s lifetime.

Reported features include: hypoinsulinemic hypoglycemia, hypoglycemic seizures, developmental delay, hemihypertrophy (asymmetric overgrowth of one side of the body), overgrowth / macrosomia, proptosis, macroglossia, and acanthosis nigricans.

Is overgrowth or weight gain related to the AKT2 mutation, or to its treatment? ▾

Both are possible contributors, and researchers do not yet know how much each plays a role. The AKT2 pathway is directly involved in regulating cell growth, not just glucose metabolism — so the constitutive activation seen in AKT2 E17K may itself drive the overgrowth (increased body or tissue size) reported in some patients.

At the same time, many patients require frequent, carbohydrate-rich feeding — including uncooked cornstarch and modified starches — to prevent hypoglycemia, and this nutritional approach could independently contribute to weight gain over time.

2. Managing Hypoglycemia and Nutrition

Does fasting tolerance improve with age? ▾

Published case reports suggest that fasting tolerance in patients with AKT2 E17K is lowest in the neonatal and early childhood period.

Many neonates without the AKT2 E17K mutation require frequent feeding to maintain safe glucose levels. Yet, as children grow, fasting intervals may gradually lengthen and episodes of hypoglycemia may become less frequent. In patients with the AKT2 E17K mutation, one case report describes improvement in glucose management with age, while another demonstrates how optimized nutritional management, including with waxy maize heat-modified starch, could improve fasting tolerance.

How long can patients usually fast safely? ▾

Fasting tolerance varies considerably between patients.

Published case reports suggest that some individuals eventually achieve fasting intervals of approximately 3–4 hours with optimized nutritional treatment. However, age, disease severity, and nutritional management all influence fasting tolerance, making it difficult to define a typical pattern.

Why do some children require gastric tube placement and continuous overnight feeding? ▾

Many infants and young children are initially managed with enteral (tube) feeding, via a nasogastric tube or a surgically placed gastrostomy tube (G-tube). Tube feeding provides a steady and accessible source of glucose and reduces the risk of hypoglycemia. This is especially true at night, when continuous overnight feeds can prevent dangerous hypoglycemic episodes.

Why do some children continue overnight feeding even after daytime fasting improves? ▾

Nighttime presents a unique challenge because the fasting period is much longer than during the day.

Even when a child can safely tolerate several hours between meals while awake, maintaining adequate glucose levels throughout an entire night's sleep may remain difficult. Continuous overnight feeding can provide a steady source of glucose without requiring repeated nighttime feeds.

Should continuous glucose monitoring (CGM) be considered? ▾

Continuous glucose monitoring (CGM) may be recommended for patients with AKT2 E17K, especially those with a history of hypoglycemic seizures.

CGM systems can provide early warning of falling glucose levels, including during sleep, and help families and clinicians better understand glucose patterns and the effectiveness of nutritional interventions.

What is uncooked cornstarch (UCCS), and why is it used? ▾

Uncooked cornstarch (UCCS) is a slowly digested carbohydrate that releases glucose gradually over time.

In reported AKT2 patients, UCCS has been helpful in extending fasting intervals and reducing the risk of hypoglycemia.

What is Glycosade®, and can it help? ▾

Glycosade® is a modified starch product designed to release glucose more slowly and over a longer period than traditional uncooked cornstarch.

Published experience in AKT2 E17K is limited, with one case in a 4-year-old child reporting extended nighttime fasting tolerance, and another case in a 1-year-old child not reporting any difference. One possible explanation for this age discrepancy is that expression of pancreatic amylase is substantially reduced in infancy, impairing starch digestion. In glycogen storage diseases, Glycosade has been studied and used successfully in children from around 2 years of age under specialist supervision.

Does every patient respond the same way to nutritional interventions? ▾

No. The response to feeding schedules, cornstarch therapy, Glycosade, and other nutritional strategies appears to vary between patients.

Since so few individuals have been identified worldwide, it is not yet possible to predict which approaches will work best for a particular patient.

3. Development, Presentation & Long-term Outcomes

Does AKT2 E17K always cause developmental delay? ▾

No. Developmental delay has been reported in some patients, but not in all individuals described in the medical literature. The severity and type of developmental challenges vary considerably between patients.

Is developmental delay caused by the genetic mutation itself? ▾

The relationship between the AKT2 E17K mutation and developmental delay that was found in some patients is not yet fully understood. However, current evidence suggests that recurrent or severe hypoglycemia may worsen developmental outcomes.

Does every patient have the same clinical presentation? ▾

No. Although patients share the same AKT2 mutation, the clinical presentation can differ substantially between individuals. Some features are common, while others are reported only in a subset of patients.

Why does the clinical presentation differ between patients with the same genetic mutation? ▾

Researchers do not yet fully understand why some individuals are more severely affected than others. One possible explanation is mosaicism, where different tissues may carry different proportions of cells affected by the mutation. Other factors, including genetic background, disease severity, and differences in medical management, may also influence how the condition presents.

What do we know about long-term outcomes? ▾

Long-term outcomes remain one of the largest unanswered questions about AKT2 E17K. Since so few patients have been identified worldwide, only limited information is available regarding adulthood, long-term metabolic health, and lifelong complications.

Follow-up of two patients at age 17 showed that hypoglycemia had become less severe compared with early childhood, although fasting tolerance varied considerably: one maintained normal glucose through an overnight fast, while the other still developed symptomatic hypoglycemia after approximately three hours. Despite increased body fat, neither patient showed evidence of fatty liver, high triglycerides, or increased liver fat production.

A 30-year follow-up of the original MORFAN patient, the only follow-up study into adulthood identified in the literature, found that overall intellectual abilities remained largely within the normal range. However, selective difficulties in psychomotor speed and executive function were identified. The patient also developed intracranial meningiomatosis and renal hamartomas requiring surgical treatment, leading the authors to highlight tumor development as a potential long-term concern and the possible importance of regular oncological surveillance.

You know things that aren't written anywhere.

Every family that lives with this condition has practical knowledge — patterns, strategies, observations — that no paper has captured. If you're one of those families, this section is being built for and with you.

Research Hub

Published literature
on AKT2 E17K (p.Glu17Lys)

There are 12 independent and genetically-confirmed published cases of the AKT2 E17K mutation and 1 genetically-confirmed yet unpublished case, making 13 known patients known to date to our group. Here are all the published case reports organized by the groups of patients each of them describe.

Sort by / /
12 articles · 9 patient groups
Note: Single AKT2 p.Glu17Lys patient; first reported successful use of waxy maize heat-modified starch (Glycosade®) to prolong fasting periods in a 4-year-old patient.
Treatment of hypoglycemia due to a rare pathogenic variant in AKT2 with waxy maize heat-modified starch
From the abstract:Following in-hospital administration of waxy maize heat-modified starch at age 4 years, the patient remained euglycemic overnight — despite a previous report showing no benefit from this approach in an infant with the same mutation.
Parker M, Yau D. Treatment of hypoglycemia due to a rare pathogenic variant in AKT2 with waxy maize heat-modified starch. Clin Case Rep. 2024;12(2):e8473. doi:10.1002/ccr3.8473
View source ↗
Note: Three related papers for the same patient group — the 2004 index patient, the 2011 genetic identification of the index proband plus two additional patients, and the 2017 follow-up and metabolic characterization.
Hypoketotic hypofattyacidaemic hypoinsulinaemic hypoglycaemia in a child with hemihypertrophy? A new syndrome
From the abstract:Reports a novel case of a child with hemihypertrophy and severe, persistent hypoketotic, hypofattyacidaemic, hypoinsulinaemic hypoglycaemia — with no big pro-IGF2 forms or circulating insulin-receptor antibodies found.
Hussain K, Bodamer OAF, Cameron FJ, et al. Hypoketotic hypofattyacidaemic hypoinsulinaemic hypoglycaemia in a child with hemihypertrophy? A new syndrome. Horm Res. 2004;61(5):222-227. doi:10.1159/000076553
View source ↗
An activating mutation of AKT2 and human hypoglycemia
From the abstract:Identifies the causative AKT2 mutation shared by three patients with severe hypoglycemia, establishing the molecular basis of the syndrome and showing the mutation was not present in either parent.
Hussain K, Challis B, Rocha N, et al. An activating mutation of AKT2 and human hypoglycemia. Science. 2011;334(6055):474. doi:10.1126/science.1210878
View source ↗
Constitutive activation of AKT2 in humans leads to hypoglycemia without fatty liver or metabolic dyslipidemia
From the abstract:A long-term metabolic characterization of two previously reported patients at age 17, showing the mutation produces hypoglycemia and suppressed fatty acid release without fatty liver, hypertriglyceridemia, or elevated hepatic lipogenesis.
Minic M, Rocha N, Harris J, et al. Constitutive activation of AKT2 in humans leads to hypoglycemia without fatty liver or metabolic dyslipidemia. J Clin Endocrinol Metab. 2017;102(8):2914-2921. doi:10.1210/jc.2017-00768
View source ↗
Note: AKT2 p.Glu17Lys/E17K patient reported as a de novo mosaic case.
Activating AKT2 mutation: hypoinsulinemic hypoketotic hypoglycemia
From the abstract:Describes the second reported case of an activating AKT2 mutation. Genetic testing identified a de novo mosaic c.49G→A (p.E17K) mutation, consistent with the clinical and biochemical phenotype.
Arya VB, Flanagan SE, Schober E, Rami-Merhar B, Ellard S, Hussain K. Activating AKT2 mutation: hypoinsulinemic hypoketotic hypoglycemia. J Clin Endocrinol Metab. 2014;99(2):391-394. doi:10.1210/jc.2013-3228
View source ↗
Note: Adolescent presentation with the same activating AKT2 variant.
Case report: hypoinsulinaemic hypoketotic hypoglycaemia due to an activating variant in AKT2
From the abstract:Reports a new patient with the same AKT2 alteration and dysmorphic features. To the authors' knowledge, this is the first report using continuous glucose monitoring (CGM) for diagnosis and follow-up in this condition.
Sayol-Torres L, Campos-Martorell A, Sala-Coromina J, Fernández-Álvarez P, Lasa-Aranzasti A, Clemente León M. Case report: hypoinsulinaemic hypoketotic hypoglycaemia due to an activating variant in AKT2. J Clin Res Pediatr Endocrinol. Published online August 11, 2025. doi:10.4274/jcrpe.galenos.2025.2025-3-26
View source ↗
Note: Familial AKT2 p.Glu17Lys cases in two brothers; variant inherited from their unaffected mosaic father.
Efficacy and safety of sirolimus therapy in familial hypoinsulinemic hypoglycemia caused by AKT2 mutation inherited from the mosaic father
From the abstract:Describes the metabolic and hormonal profile before and during sirolimus treatment in two brothers with an AKT2 mutation inherited from their mosaic father, who showed low-level mosaicism in sperm.
Dushar M, Nowaczyk J, Pyrżak B, et al. Efficacy and safety of sirolimus therapy in familial hypoinsulinemic hypoglycemia caused by AKT2 mutation inherited from the mosaic father. Eur J Med Genet. 2021;64(12):104368. doi:10.1016/j.ejmg.2021.104368
View source ↗
Note: Infantile MORFAN phenotype due to a de novo AKT2 p.Glu17Lys/E17K mutation.
MORFAN syndrome: an infantile hypoinsulinemic hypoketotic hypoglycemia due to an AKT2 mutation
From the abstract:Reports a child with hypoinsulinemic hypoglycemia and distinctive facies, diagnosed with the previously described MORFAN syndrome. Whole-exome sequencing revealed a de novo AKT2 mutation, expanding the phenotypic spectrum to include MORFAN characteristics.
Garg N, Bademci G, Foster J II, Sıklar Z, Berberoglu M, Tekin M. MORFAN syndrome: an infantile hypoinsulinemic hypoketotic hypoglycemia due to an AKT2 mutation. J Pediatr. 2015;167(2):489-491. doi:10.1016/j.jpeds.2015.04.069
View source ↗
Note: AKT2 p.Glu17Lys case with dysmorphic features and treatment comparison.
Facial dysmorphic features in a patient with nonketotic hypoglycemia and a pathogenic variant in the AKT2 gene
From the abstract:Reports a new patient with dysmorphic features and the same activating AKT2 alteration. To the authors' knowledge, this is the first report using waxy maize heat-modified starch (WMHMS) in this condition; response was similar to uncooked cornstarch with no adverse effects.
Ochoa Molina MF, Poggi H, De Toro V, Mendoza C, Hussain K. Facial dysmorphic features in a patient with nonketotic hypoglycemia and a pathogenic variant in the AKT2 gene. AACE Clin Case Rep. 2021;8(3):109-112. doi:10.1016/j.aace.2021.11.006
View source ↗
Note: AKT2 c.49G>A p.E17K mosaic case identified in China; abstract available in English and Chinese.
Hypoglycemia caused by AKT2 gene mutation: a case report and literature review
From the abstract:Describes a 15-month-old girl with hypoglycemia, undetectable insulin, low ketones and free fatty acids, and limb asymmetry, found to carry a mosaic AKT2 c.49G>A (p.E17K) variant. With a high-carbohydrate diet and bedtime uncooked cornstarch, hypoglycemic episodes became less frequent, and growth and development were normal after 18 months of treatment. The authors note it as the first reported case from China.
Du M, Song F, Chen X. Hypoglycemia caused by AKT2 gene mutation: a case report and literature review. Chinese Journal of General Practitioners. 2021;20(11):1171-1175. doi:10.3760/cma.j.cn114798-20210627-00498
View source ↗
Note: The 1993 MORFAN description and the 2026 paper are grouped because the 2026 paper is a long-term, molecularly confirmed follow-up of the same original patient.
MORFAN: a new syndrome characterized by mental retardation, pre- and postnatal overgrowth, remarkable face and acanthosis nigricans in 5-year-old boy
Seemanová E, Rüdiger HW, Dreyer M. MORFAN: a new syndrome characterized by mental retardation, pre- and postnatal overgrowth, remarkable face and acanthosis nigricans in 5-year-old boy. Am J Med Genet. 1993;45(4):525-528. doi:10.1002/ajmg.1320450424
View source ↗
A more precise description of the AKT2-related hypoinsulinemic hypoglycemia and overgrowth syndrome phenotype, formerly described under the MORFAN acronym
From the abstract:The syndrome was initially described over 30 years ago under the MORFAN acronym. A comprehensive 30-year follow-up of the same patient enabled detailed exploration of the syndrome's clinical trajectory, spanning three decades of observation.
Turnovec M, Bubeníková A, Rýdlo O, et al. A more precise description of the AKT2-related hypoinsulinemic hypoglycemia and overgrowth syndrome phenotype, formerly described under the MORFAN acronym. Am J Med Genet A. Published online March 23, 2026:e70138. doi:10.1002/ajmg.a.70138
View source ↗
Join the Network

There are only a handful of families
in the world who understand this.

We're trying to find all of them — and connect them with the clinicians and researchers who can help.

Who we're looking for

This network is for everyone
who touches this condition.

👨‍👩‍👧
Families
Parents and caregivers of someone with AKT2 E17K (p.Glu17Lys). Your day-to-day experience holds knowledge that no paper has captured — about nutrition, monitoring, development, and life with this condition. You are the reason this network exists.
🩺
Clinicians
Endocrinologists, geneticists, metabolic dietitians, and other specialists who have encountered this condition. Your clinical observations — even from a single case — are valuable to every other family and to the research community.
🔬
Researchers
Scientists working on AKT2, the PI3K/mTOR/AKT signaling pathway, rare metabolic disorders, or any of the therapeutic approaches described on this site — including ASO therapy, glucagon-based treatments, or CRISPR-based gene editing. If your work touches this biology, we'd like to connect. AKT2 E17K may be rare, but the pathway is not.

Get in touch

We're looking to connect with more families, clinicians, and researchers who understand this condition — please reach out to us by sending an email to: contact@akt2hope.org

About Us

Why this initiative
exists.

Who we are, and why we built this.

Our story

Why this initiative exists

We're a family. Our baby was born with AKT2 E17K, an ultra-rare condition with only a handful of known patients worldwide. When we got the diagnosis, we found scattered research but no single place connecting the families, clinicians, and researchers who understand it. So we built one — to gather what's known, share it openly, and connect everyone this condition touches.

Dr. Shai Fuchs is a pediatric endocrinologist and principal investigator at Safra Children's Hospital, Sheba Medical Center. His clinical and laboratory work brings together pediatric endocrinology and research on hepatic metabolic regulation. In collaboration with Sheba's lab for RNA therapies, this collaborative venture is exploring the biology of AKT2 E17K and possible therapeutic approaches. The initiative aims to help families find one another and connect with clinicians and researchers.

The website was reviewed for medical and scientific accuracy by Dr. Shai Fuchs, MD, PhD and Dr. Michael Shulman, MD, BEng from Sheba Medical Centre. The information provided on this website does not constitute medical advice and is meant for community building and research purposes only. All medical decisions belong to your own treatment team.