Table 1 Phenotypes of the patients.

From: Neutropenia and intellectual disability are hallmarks of biallelic and de novo CLPB deficiency

 

P1, female

P2, female

P3, male

P4, female

P5, female

P6, male

Ethnicity, country of residence

White, Germany

White, Austria

White, Germany

White, USA

White, Australia

White, USA

CLPB (NM_030813.4) de novo

c.1211A>C; [=], p.Lys404Thr; [=]

c.[1280C>T]; [=], p.[Pro427Leu]; [=]

c.[1678G>A];[=], p[Gly560Arg];[=]

c.[1678G>A];[=], p[Gly560Arg];[=]

c.[1681C>T];[=], p[Arg561Trp];[=]

c.[1681C>T];[=], p[Arg561Trp];[=]

Current age (years)

3.0

19 months (deceased)

7.0

7.8

12.4

5.3

Presenting age: signs & symptoms

Neonatal: AMC, 18 months: seizures

Neonatal: seizures, virtually no development

Neonatal: oral and perianal abscesses, 15 months neutropenia

Neonatal: sepsis, neutropenia

12 months: recurrent infections, neutropenia, DD

Neonatal: umbilical cord stump infection

Lowest ANC value (1.5–8.5 × 109/ml)

Normal range

0.6–0.9 (during infections)

0.7–1.2

0.0–0.1

0.4

0.1

Neutropenia

No

Moderate during infections

Moderate, controlled with GCSF

Severe, HSCT 15 months

Severe, not controlled with GCSF

Severe, HSCT 5 years

Other hematological issues

No

No

Mild anemia

Intermittent mild anemia

Mild anemia

Normochromic anemia, mild anisopoikilocytosis

Best motor achievement

Walking independently, running with assistance

Virtually no development

Sitting with assistance, nonambulatory

Ambulatory with a wide based gait not able to run, able to jump with both feet off the ground

Currently: can sit upright in a wheel chair

Milestones on time, able to run, jump, go up/down stairs, well coordinated

Best language achievement

Speaks 50 words, starts 2 word sentences, uses gestures

Virtually no development

Nonverbal

Verbal communication with 1–2 word sentences not able to converse still makes progress

10–20 words, receptive > expressive language, uses communication device

Full comprehension, speaks in full sentences, articulation deficits, mild speech delay

Loss of skills, age at loss

No

Virtually no development

Yes, lost standing and walking skills; some steps with help at age 3 years, no further development since

Yes, after BMT e.g., loss of “animal sounds”

Yes, lost ability to use walking frame at 9.5 years

No

Muscle tone

Generalized hypotonia, no spasticity

Truncal and oral hypotonia with limb spasticity

Truncal hypotonia with limb spasticity

Mild truncal hypotonia with limb spasticity

Truncal hypotonia with limb spasticity

Normal

Severity of DD/ID

Moderate

Severe

Severe

Moderate

Moderate

Mild

Seizures, type

Myoclonic, tonic–clonic, atypical absences, not controlled

Generalized, apnea/bradycardia, hyperextension of the trunk, not controlled

Absences, sometimes with myoclonic aspects, controlled

Atypical absence seizures, controlled

Atypical absence-like episode, not completely controlled

No

MRI alterations

12 months: periventricular white matter alterations

Neonatal: normal; 17 months: mild cerebellar atrophy, slight T2-hyperintensities in the central white matter

3 years: mild global atrophy, diffusely abnormal white matter signal

5 years: mild cerebellar atrophy; periatrial and periventricular FLAIR signal abnormality with associated volume loss

15 months: diffusely elevated white matter signal, including cerebellar white matter, indicating delayed myelination

7 years: additionally supratentorial atrophy and abnormal basal ganglia signal (T2)

5 years: hazy, biparietal periventricular and deep white matter signal; focal thinning of posterior body of corpus callosum

Microcephaly, secondary

+

+

+

+

urinary 3-MGA

+ (mild)

+ (mild)

+ (high)

+ (moderate)

+ (mild)

+ (high)

  1. AMC arthrogryposis multiplex congenital, BMT Bone Marrow Transplantation, DD developmental delay, FLAIR fluid-attenuated inversion recovery, GCSF granulocyte colony stimulating factor, HSCT hematopoietic stem cell transplantation, ID intellectual disability, MRI magnetic resonance image.