Rhabdomyolysis and Metabolic Myopathy

Gene: AIFM1

Green List (high evidence)

- Onset is in utero or in infancy
- Affected individuals typically present with hypotonia, impaired psychomotoro development with decreased enzymatic activity, specifically in skeletal muscle or fibroblasts

6 individuals from 3 unrelated families presented with hypotonia with muscle weakness and increased plasma lactate and a hemizygous mutation in AIFM1 causative of Combined oxidative phosphorylation deficiency 6 (COXPD6).

PMID: 20362274
2 individuals (first cousins) from one family with Hypotonia and hypo-areflexia and increased lactate in plasma and both individuals carried a hemizygous deletion
In vitro studies showed that in the presence of the deletion, the inner mitochondrial membrane is destabilised causing damage to the respiratory chain structure and activities.

PMID: 22019070
2 brothers (one deceased) with hyptonia and symptoms of hypertrophic cardiomyopathy (HCM) and complete cytochrome C oxidase deficiency on a histochemistry staining.

PMID: 26173962
2 individuals from one family (cousins) with hemizyggous mutation in AIFM1
Both presented with hypotonia with muscle weakness and increased plasma lactate
Segregation study showed unaffected mother was a carrier for the hemizygous mutation
Sources: Other

Created: 9 May 2023, 6:18 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Combined oxidative phosphorylation deficiency 6 (COXPD6) (MIM#300816); Encephalamyopathy, Mitochondrial, X-Linked

Publications

• 20362274
• 22019070
• 26173962

Comment when marking as ready: Myopathy as part of metabolic condition.

Created: 10 Jun 2020, 8:44 p.m. | Last Modified: 10 Jun 2020, 8:44 p.m.

Panel Version: 0.140

Green List (high evidence)

PMID: 31523922 - 1 large family (7 male patients) with AIFM1-related neuropathy (Cowchock syndrome). Patients had variable age of onset (18 months - 39 years), but most had onset in adolescent years (14-17 years old). A missense variant segregated within the family, has been previously reported.

PMID: 31783324 - Adult-onset ataxic sensory neuropathy and hearing impairment. in a Japanese patient, reported symptoms at 35 years old. Unsteady gait developed in his late 40s. Patient had a missense variant.

PMID: 28299359 - A deceased male child with congenital lactic acidosis, mitochondrial encephalopathy, myopathy and axonal degeneration. Patient had a missense. Not noted if maternally inherited or de novo.

PMID: 25934856 - a male patient with mitochondrial encephalopathy with onset at 1 year old where they experienced walking difficulties. Patient had a missense, maternally inherited.

Summary: some reports of paediatric disease but very few/none for congenital onset.

Created: 10 Jun 2020, 3:48 a.m. | Last Modified: 10 Jun 2020, 3:48 a.m.

Panel Version: 0.138

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Cowchock syndrome 310490; Combined oxidative phosphorylation deficiency 6 300816

Publications

• PMID: 31523922
• 31783324
• 28299359
• 25934856

Green List (high evidence)

At least 3 families reported with myopathy as a feature of the condition. Paediatric onset.
Sources: Expert Review

Created: 24 Feb 2020, 2:08 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Combined oxidative phosphorylation deficiency 6 MIM#300816

Publications

• 25583628
• 28299359