The TEMPO (Tracing the Effect of the MC4 Pathway in Obesity) Registry

Potential patients will be referred to coordinating centers by their healthcare provider
(treating physician, diagnosing physician or primary care physician) and if eligible will be
invited to enroll in the registry. The Registry Coordinating Center will be responsible for
obtaining consent from adult patients and caregivers of minor patients (as well as assent
from minors when appropriate), screening patients and enrolling them in the registry.

The registry will capture data entered by the patient, the patient's healthcare provider, and
the patient's caregiver using online (electronic) survey tools administered at baseline, and
annually thereafter. The patient's healthcare provider will complete the baseline Healthcare
Provider survey tool, reporting the patient's baseline demographics, medical history,
clinical information, and disease characteristics. The patient and caregiver will complete
their dedicated baseline survey tools answering questions on the impact of disease on their
everyday life. Survey tools include questions on patient and caregiver demographics, patient
physical activity, patient food and hunger episodes, patient quality of life, and caregiver's
perspective of disease burden on the family. Registry patients, caregivers, and healthcare
providers will be contacted annually (approximately every 12 months) by the Registry
Coordinating Center to complete an online follow-up survey tool including a smaller subset of
questions from the baseline survey tools.

Inclusion Criteria:

1. Extreme obesity patients aged 2 years and older.

2. Extreme obesity defined as:

1. BMI > 40 kg/m2 in patients 18 years of age or older.

2. BMI value that is >1.4 times the corresponding age/gender 95th percentile value
in patients who are 2 through 17 years of age.

3. At least one of the following genotypes:

1. Bi-allelic (homozygous or compound heterozygous) POMC, PCSK1, LEPR variants
leading to the physician-confirmed diagnosis of either POMC or LEPR deficiency
obesity.

2. The presence of high-confidence, high-impact genetic variations (homozygote,
compound heterozygote, heterozygote or composite heterozygote [i.e., heterozygous
variants in more than a single gene]) in these same 3 genes (POMC, PCSK1 and
LEPR) associated with the clinical presentation of extreme obesity

3. The presence of other high-confidence, high-impact genetic variations
(homozygote, compound heterozygote, heterozygote or composite heterozygote in the
MC4R gene or other upstream MC4R-pathway genes and selected variants downstream
in the MC4R-pathway (Table 1) that are carried by extreme obesity patients who do
not demonstrate specific syndromic obesity clinical presentations. Selected
Bardet-Biedl syndrome (BBS1 through BBS21) genetic variants or Alström syndrome
(ALMS) genetic variants possibly contributing to non-syndromic forms of clinical
extreme obesity will be eligible for enrollment.

4. Study participant and/or parent or caregiver can understand and comply with the
requirements of the study, and able to understand and sign the written informed
consent (IC)/assent, after being informed about the study.

Exclusion Criteria:

1. Patients with syndromic forms of obesity such as Bardet-Biedl syndrome or Alström
syndrome. These patients will be referred to existing registries for these specific
syndromic obesity (e.g., Clinical Registry in Bardet-Biedl syndrome [CRIBBS] for BBS
patients).

2. Individual is, in the opinion of the study investigator, not suitable to participate
in the study.