MEHMO Syndrome

Last update 08 May 2025

Basic Info

Synonyms

Intellectual disability, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, obesity syndrome, Intellectual disability, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, obesity syndrome (diagnosis), Intellectual disability, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, obesity syndrome (disorder)

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Introduction

MEHMO syndrome has characteristics of severe intellectual deficit, epilepsy, microcephaly, hypogenitalism and obesity. Growth delay and diabetes are also present. To date, it has been described in seven boys, all of who died within the first two years of life. The causative gene has been located to the 21.1-22.13p region of the X chromosome and the syndrome appears to result from mitochondrial dysfunction.

Clinical Trials associated with MEHMO Syndrome

NCT06019182

/ RecruitingNot ApplicableIIT

Investigations of Individuals With MEHMO Syndrome or eIF2-Pathway Related Conditions

This observational natural history study will follow individuals with MEHMO (Mental disability, Epileptic seizure, Hypopituitarism/Hypogenitalism, Microcephaly, Obesity) syndrome or an eIF2-pathway related disorder, who have symptoms such as intellectual delay, seizures, abnormal hormone and blood sugar levels, and decreased motor skills.
No current treatment for these conditions is available. A major impediment to the testing of potential therapeutic interventions is the lack of well-defined outcome measures. This protocol seeks to identify biochemical and clinical markers to monitor disease progression, and better understand the natural history of these conditions.
Any person diagnosed with MEHMO syndrome or related conditions, who can travel to the NIH Clinical Center can participate in this study.
The study involves:
* General health assessment and evaluation
* Imaging studies
* Laboratory tests
* Collection of blood, urine, spinal fluid, skin biopsy.

Start Date23 Oct 2023

Sponsor / Collaborator

National Institute of Child Health & Human Development

100 Clinical Results associated with MEHMO Syndrome

100 Translational Medicine associated with MEHMO Syndrome

0 Patents (Medical) associated with MEHMO Syndrome

Literatures (Medical) associated with MEHMO Syndrome

01 Sep 2023·Journal of Structural Biology

Binding of human Cdc123 to eIF2γ

Article

Author: Mechulam, Yves ; Schmitt, Emmanuelle ; Fagart, Jérôme ; Cardenal Peralta, Cristina ; Neumann-Arnold, Lea ; Seufert, Wolfgang ; Vandroux, Paul ; Panvert, Michel

Eukaryotic initiation factor 2 (eIF2) plays a key role in protein synthesis and in its regulation. The assembly of this heterotrimeric factor is facilitated by Cdc123, a member of the ATP grasp family that binds the γ subunit of eIF2. Notably, some mutations related to MEHMO syndrome, an X-linked intellectual disability, affect Cdc123-mediated eIF2 assembly. The mechanism of action of Cdc123 is unclear and structural information for the human protein is awaited. Here, the crystallographic structure of human Cdc123 (Hs-Cdc123) bound to domain 3 of human eIF2γ (Hs-eIF2γD3) was determined. The structure shows that the domain 3 of eIF2γ is bound to domain 1 of Cdc123. In addition, the long C-terminal region of Hs-Cdc123 provides a link between the ATP and Hs-eIF2γD3 binding sites. A thermal shift assay shows that ATP is tightly bound to Cdc123 whereas the affinity of ADP is much smaller. Yeast cell viability experiments, western blot analysis and two-hybrid assays show that ATP is important for the function of Hs-Cdc123 in eIF2 assembly. These data and recent findings allow us to propose a refined model to explain the mechanism of action of Cdc123 in eIF2 assembly.

01 Feb 2022·European Journal of Medical GeneticsQ4 · MEDICINE

mRNA analysis revealed a novel pathogenic EIF2S3 variant causing MEHMO syndrome

Q4 · MEDICINE

Article

Author: Demina, Nina ; Skoblov, Mikhail ; Serzhanova, Victoria ; Ivanova, Nadezda ; Guseva, Darya

EIF2S3 pathogenic variants have been shown to cause MEHMO syndrome - a rare X-linked intellectual disability syndrome. In most cases, DNA diagnostics of MEHMO syndrome is performed using exome sequencing. We describe two cousins with profound intellectual disability, severe microcephaly, microgenitalism, hypoglycemia, epileptic seizures, and hypertrichosis, whose clinical symptoms allowed us to suspect MEHMO syndrome. To confirm this diagnosis, we designed an mRNA analysis for the EIF2S3 gene. It is a cost-effective method to detect coding sequence variants in multi-exonic genes, as well as splicing defects and allelic imbalance. Our mRNA sequence analysis revealed a novel EIF2S3 variant c.820C>G in both cousins. We also found the same variant in female family members in the heterozygous state. To investigate the pathogenicity of the c.820C>G variant, we performed expression analysis, which showed that the DDIT3 transcript level was significantly increased in the patient relative to the controls. We, thus, demonstrate that mRNA analysis is an efficient tool for performing genetic testing in patients with distinct phenotypic features.

01 Jun 2021·Brain and Development

Ketogenic diet for refractory epilepsy with MEHMO syndrome: Caution for acute necrotizing pancreatitis

Author: Maruo, Yoshihiro ; Kumada, Tomohiro ; Matsui, Katsuyuki ; Yamada, Mamiko ; Kosaki, Kenjiro ; Inoue, Kenji ; Shibata, Minoru ; Suzuki, Hisato ; Mori, Mioko ; Nozaki, Fumihito

BACKGROUNDThe MEHMO (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity) syndrome, which is caused by a hemizygous variant in the EIF2S3 gene on chromosome Xp22, is associated with significant morbidity and mortality. Refractory epileptic seizures and glucose dysregulation are characteristic manifestations of the MEHMO syndrome, which can often diminish patients' quality of life.CASEA 5-year-old boy was referred to our hospital because of profound intellectual disability, micropenis, cryptorchidism, central hypothyroidism, and microcephaly. He had neonatal hypoglycemia at birth and later experienced refractory epileptic seizures and developed obesity and insulin-dependent diabetes. A diagnosis of MEHMO syndrome was established on the basis of the patient's clinical manifestations and de novo novel missense variant in the EIF2S3 gene (NM_001415.3:c.805 T > G) that was detected through whole-exome analysis. Although the patient's refractory seizures and diabetes had been well controlled with a combination of ketogenic diet (KD) therapy and insulin therapy, acute fatal necrotizing pancreatitis occurred at the age of 68 months. Moreover, despite intensive care, his condition rapidly deteriorated to multiple organ failure and acute respiratory distress syndrome, resulting in death.CONCLUSIONThe pathophysiology of glucose intolerance in MEHMO syndrome remains to be elucidated; however, recent studies have suggested that EIF2S3 gene variants could lead to glucose dysregulation and β-cell damage in the pancreas. We suspect that in the present case, KD therapy led to an abnormal load on the beta cells that were damaged owing to eIF2γ dysfunction. Therefore, the adverse effects of KD in patients with MEHMO syndrome should be considered.

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