P 1011. Think Unusual—Developmental Delay Plus: Multimodal Diagnosis of Menkes’ Syndrome

Background: Developmental disorders and neurological diseases of childhood are caused by a variety of factors. Different disease entities show a mimicry of similar symptoms, so that the collection of conspicuous findings is of decisive value. In addition, natural development and maturation of the child’s organism and the presence of possible minor forms of various disease spectra must be taken into account.

Case Report: A 3-year-old boy, leading symptoms: frequent infections, combined developmental delay, muscle hypotonia, epilepsy, and cutis laxa.

Medical history: In infancy and early infancy, repeated infections of the upper airways and multiple pneumoniae, partly with respiratory insufficiency.

Recurrent headaches, a questionable generalized tonic-clonic seizure at the age of almost 3 years. Delayed achievement of all milestones.

Family history: Parents healthy, two healthy older brothers. Delay in development of unclear cause in two paternal cousins.

Clinical characteristics: Lateral sloping eyelid axes, soft, full cheeks. Cutis laxa with pale, dry integument. Hair a little shaker, ashy-dark brown, not brittle. Abdomen protruding. Myopathic, hypomimic facies, generalized muscular hypotonia, narrow muscle profiles, regular muscular reflexes.

Paraclinic: Borderline serum levels for copper (12.6 and 12.0 µmol/L [Ref.: 12.6–23.6]) and coeruloplasmin (0.249 and 0.293 g/L [Ref. 0.2–0.6 g/L]); urine copper within normal values (0.27 µmol/d [Ref. 0.16–0.94]).

Imaging: Cranial magnetic resonance imaging (cMRI): large caliber and elongated structure of all intracranial arterial vessels, large calibers of vena basalis Rosenthal, sinus rectus; angiography: Tortuositas A. vertebralis, Aa. Caroten’s internal, intracranial arteries. Deformed confluens sinuum and sinus transversus. No calcifications (cCT). In whole-body MRI detection of tortuosity also of the extracranial vessels. EEG focus right centroparietal, during tiredness and sleep generalized paroxysms.

Genetics: Pathogenic hemizygous mutation in the ATP7A gene (X-chromosomal recessive) (NM_000052.6:c.4123+3A>T, Intron 21). ATP7A encodes a copper transport p-type ATPase.

Therapy: Start of copper histidine s.c. weekly, levetiracetam, supportive physiotherapy, ergotherapy, and speech therapy. Multiprofessional care, for example, in the social pediatric center and through the specialized outpatient palliative service for children (SAPV).

Conclusion and Discussion: In addition to frequent leading symptoms such as muscle hypotonia, developmental delay, and repeated infections, a cutis laxa was an unusual finding in the presented case. Secure classification of disease and the initiation of therapy succeeded not until MRI and genetic testing were performed. The highly pathological MRI indicated a higher degree of connective tissue disease, the diagnosis of Menke’s syndrome itself was made genetically. The milder clinical manifestation is most likely explained by the simultaneous presence of the defective copper transport protein and a functional wild type.